Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
Discuss the article on the Forums.

Medscape Discusses Fluge and Mella FIndings of PDH Impairement

Discussion in 'Latest ME/CFS Research' started by Never Give Up, Jan 13, 2017.

  1. Never Give Up

    Never Give Up Collecting improvements, until there's a cure.

    Messages:
    957
    Likes:
    3,955
    Great article. It discusses the findings and the bigger study and Anthony Kamaroff brings his critical eye to the findings.

     
    Last edited: Jan 13, 2017
    leokitten, Aroa, Woolie and 32 others like this.
  2. hixxy

    hixxy Senior Member

    Messages:
    1,130
    Likes:
    1,304
    Australia
  3. Never Give Up

    Never Give Up Collecting improvements, until there's a cure.

    Messages:
    957
    Likes:
    3,955
    MEMum likes this.
  4. hixxy

    hixxy Senior Member

    Messages:
    1,130
    Likes:
    1,304
    Australia
    It's a the url from Google search results so tricks them into thinking you're clicking through from Google. This avoids the annoying login prompt to access the content when linked directly.
     
    Woolie, MeSci, MEMum and 5 others like this.
  5. Ysabelle-S

    Ysabelle-S Highly Vexatious

    Messages:
    523
    Likes:
    4,041
    Excellent article! Thanks for posting. :)
     
  6. eljefe19

    eljefe19

    Messages:
    483
    Likes:
    639
    Comment from the medscape article. Any thoughts from anyone?
     
    Laelia, Woolie, merylg and 3 others like this.
  7. nandixon

    nandixon Senior Member

    Messages:
    832
    Likes:
    2,083
    The Fluge & Mella results, when you integrate the metabolic findings with the gene expression findings, are showing that the mTOR (mTORC1) pathway is likely under-activated. This is probably the most important thing to understand, I think.

    In most other diseases like cancer, autoimmune diseases (MS, SLE, etc.) and degenerative diseases, mTORC1 seems to be over-activated.

    So for the first time we perhaps can see just how different ME/CFS is.

    Given that there's a lot of research right now in these other diseases focusing on trying to reduce mTOR/mTORC1 activity, perhaps if those researchers studied ME/CFS they might gain some better insight.
     
    sue la-la, Woolie, Cohen2 and 7 others like this.
  8. eljefe19

    eljefe19

    Messages:
    483
    Likes:
    639
    @nandixon I've been following your posts judiciously and have built a stack to activate mTorC1. I can explicate the entire stack if anyone's interested. I think Ketamine is the holy grail of mTor. Dr. Goldstein said it was his number one favorite drug for ME/CFS. Will report back. So far, no dramatic results. Still my normal ill feeling.

    Edit: Fuck it. So far my stack consists of Phosphaditic Acid, creative hcl and monohydrate, pantethine and pantothenic acid, Leucine and glutamine 2x a day, and high dose Niacinamide for Ceramide production. I want to add the following; Rifampin (possibly upregulates sphingolipids), Ketamine (mTor and AMPA), Florinef (adolosterone and mTor), Sarcosine and/or DXM (mTor), DCA (on the way).
    Am I missing anything @nandixon?
     
  9. nandixon

    nandixon Senior Member

    Messages:
    832
    Likes:
    2,083
    @eljefe19

    I don't think I would stack anything at the outset. At least initially I would try things one at a time to see what is happening with each supplement. You might be helping things in one way and hurting them in another, and if there's a problem you won't know what's doing what.

    And a lot of things that sound good in theory may not work at all or even do the opposite in practice.

    Remember too that there is no supplement, vitamin or drug that only does one thing in the body. Everything has dozens or even hundreds of different effects. Various antibiotics, for example, are not just antibiotics but can potentially do many other things. And some are actually best-in-class for these other things. (Rifampin, for example, is stellar at upregulating a particular transporter that may be beneficial in some people and a disaster in others.)

    An even if you do find something helpful, a resetting back to homeostasis is a big problem in ME/CFS. Most of us may ultimately need something like rituximab to really help (assuming the current trial has good results)

    Personally, I would wait and see what they find and say when you visit OMI.
     
    sue la-la, rosie26, MeSci and 9 others like this.
  10. eljefe19

    eljefe19

    Messages:
    483
    Likes:
    639
    @nandixon thanks for the advice! I definitely do not take a scientific approach. More of a cowboy shotgun approach. I've never had a horror story reaction. Most supps and meds had no perceptible benefit. Oxymatrine being the exception.
     
    merylg and nandixon like this.
  11. Snow Leopard

    Snow Leopard Hibernating

    Messages:
    4,615
    Likes:
    12,454
    South Australia
    The findings of the Fluge/Mela are not the central/specific characteristics of this illness, they are downstream effects, as such, they cannot be used as specific biomarkers. On the other hand, the findings give clues to what is going wrong, when placed in the context of other studies.

    The comment ignores the increased SIRT4 expression, which makes things a bit more complicated (since it encourages lipid anabolism). mTORC1 inhibits SIRT4 expression, hence the hypothesis mentioned above.

    Some of the specific findings, eg PDK expression (and some other genes that would be predicted given the results) has been replicated in previous studies, eg the Italian twin study currently being discussed in another thread. https://www.ncbi.nlm.nih.gov/pubmed/27676445

    Immunologic dysfunction due to gut bacteria, a chronic infection of immune cells (not necessarily B-Cells!) (but insignficant levels elsewhere), or autoimmunity remain popular hypotheses.
     
    Last edited: Jan 14, 2017
    sue la-la, trails, Woolie and 11 others like this.
  12. eljefe19

    eljefe19

    Messages:
    483
    Likes:
    639
    Thanks @Snow Leopard. I am still considering immune dysfunction and bacterial translocation, I have entire stacks dedicated to both. However I have only achieved success in certain areas of my health with supplementation. Energy level and PEM are still quite bad, so as the F&M research has been discussed I've added a few things. Your comment on SIRT4 convinced me to get off Lexapro so thank you for that. Do we know of anything that inhibits SIRT4?

    @nandixon What transporter were you referring to in regards to Rifampin?
     
  13. Tunguska

    Tunguska Senior Member

    Messages:
    507
    Likes:
    484
    Lots could be said about these, but just a warning to anyone reading about Niacinamide: high doses may completely floor you. That is their effect on me, despite that niacinamide proves time and again to be a part of any combination that benefits me. It inhibits lipolysis and essentially requires a bunch of carbs. This is clearly in conflict with the PDH inhibition. So it's possible it might necessitate high-dose thiamine or that DCA. Simultaneously, for neurotransmitters the (relative) pro-acetylcholine sides of thiamine might be balanced out by the benzo-like effects of niacinamide, such that on paper they seem to complement each other.
     
    merylg, nandixon and eljefe19 like this.
  14. eljefe19

    eljefe19

    Messages:
    483
    Likes:
    639
    @Tunguska thanks for the advice! I just ordered allithiamine to take alongside the niacinamide. Do you think I should take niacinamide at night then?
     
  15. nandixon

    nandixon Senior Member

    Messages:
    832
    Likes:
    2,083
    The P-glycoprotein transporter aka the ABCB1 transporter. (Wikipedia)
     
  16. nandixon

    nandixon Senior Member

    Messages:
    832
    Likes:
    2,083
    Tunguska and eljefe19 like this.
  17. eljefe19

    eljefe19

    Messages:
    483
    Likes:
    639
    Good to know! Like I've said I'm going hard at mTorC1.
     
  18. adreno

    adreno PR activist

    Messages:
    4,841
    Likes:
    11,024
    Getting off-topic, but:

    AKG
    Carnitine
    DHEA
    Taurine
    Retinol
    MCT
     
    Last edited: Jan 14, 2017
    Tunguska and eljefe19 like this.
  19. eljefe19

    eljefe19

    Messages:
    483
    Likes:
    639
    Can I get a source for MCT? From what I could find the ketogenic diet inhibited the mTor pathway.
     
  20. adreno

    adreno PR activist

    Messages:
    4,841
    Likes:
    11,024
    https://www.ncbi.nlm.nih.gov/pubmed/23727642
     
    eljefe19 likes this.

See more popular forum discussions.

Share This Page